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Within the resurgence of socialist activity that accompanied Jeremy Corbyn's leadership of the British Labour Party between 2015 and 2019, one critical but sometimes overlooked aspect was the movement's emphasis on an expanded sense of political participation. This form of participation focused initially on an increased role for Labour Party members and forging a wide coalition with grassroots groups, but it also hinted at a future in which political participation extended not only to public ownership, but to policy-making at every level (Graeber, 2020). The aim of my research was to better understand how this expanded sense of political participation operated, how it responded to the wider status of political participation in the UK in the 21st century, and how it challenged power. I also sought to test the extent to which my militant research methodology could contribute to the movement. Militant research broadly prioritises political struggle over the academic pursuit of knowledge (Halvorsen, 2015). Within this militant research, which has been informed by the immanent philosophical tradition, I have organised with several political groups throughout Corbynism and post-Corbynism. This generated a militant research assemblage that brings together experiences, materials, and affective registers. I argue that some political participation within Corbynism and post-Corbynism can be understood as minor emergences. Within these emergences we occasionally glimpsed 'bone-deep' (Tuck, 2013) political participation. This stands in opposition to the 'nightmare' (Miessen, 2010) participation that dominates within our conjuncture. Within bone-deep participation, a radical approach to difference and unity points to where some of the key 'wins' (Cox, 2019) have challenged power.

The bone marrow is a highly specialised organ, responsible for the formation of blood cells. Despite 50 years of research, the spatial organisation of the bone marrow remains an area full of controversy and contradiction. One reason for this is that imaging of bone marrow tissue is notoriously difficult. Secondly, efficient methodologies to fully extract and analyse large datasets remain the Achilles heels of imaging-based research. In this thesis I present a pipeline for generating 3D bone marrow images followed by the large-scale data extraction and spatial statistical analysis of the resulting data. Using these techniques, in the context of 3D imaging, I am able to identify and classify the location of hundreds of thousands of cells within various bone marrow samples. I then introduce a series of statistical techniques tailored to work with spatial data, resulting in a 3D statistical map of the tissue from which multi-cellular interactions can be clearly understood. As an illustration of the power of this new approach, I apply this pipeline to diseased samples of bone marrow with a particular focus on leukaemia and its interactions with CD8+ T cells. In so doing I show that this novel pipeline can be used to unravel complex multi-cellular interactions and assist researchers in understanding the processes taking place within the bone marrow.

The February 2014 extratropical cyclonic storm chain, that im pacted the English Channel (UK) and Dawlish in particular, caused signi f icant damage to the main railway connecting the southwest region to the rest of the UK. The incident caused the line to be closed for two months, £50 million of damage and an estimated £1.2bn of economic loss. This incident highlighted the urgent need to understand the cascading nature of multi hazards involved in storm damage and their impacts on coastal railway infrastructure. This study focuses on the Dawlish railway where a seawall breach caused two months of railway closure in 2014. I used historical and con temporary data of severe weather damage and failure analysis to develop a multi-hazard risk model for the railway. Twenty-nine damage events caused significant line closure in the period 1846-2014. For each event, hazards were identified, the sequence of failures were deconstructed and a f lowchart for each event was formulated showing the interrelationship of multiple hazards and their potential to cascade. The most frequent dam age mechanisms were identified: (I) landslide; (II) direct ballast washout and (III) masonry damage. I developed a risk model for the railway which has five layers in the top-down order of: (a) Trigger (storm); (b) force gen eration; (c) common cause failure; (d) cascading failure and (e) network failure forcing service suspension. Armed with the multi-hazard cascading risk model, I go on to col late eyewitness accounts, analyse sea level data, and conduct numerical modelling in order to decipher the destructive forces of the storm. My analysis reveals that the disaster management of the event was success ful and efficient with immediate actions taken to save lives and property before and during the storm. Wave buoy analysis showed that a complex triple peak sea state with periods at 4- 8 s, 8- 12 s, and 20- 25 s was present, while tide gauge records indicated that significant surge of up to 0.8 m and wave components of up to 1.5 m amplitude combined as likely contributing factors in the event. Significant impulsive wave forces were the most likely the initiating cause of the damage. Reflections off the vertical wall caused constructive interference of the wave amplitudes that led to increased wave height and significant overtopping, our numer ical simulations suggesting up to 16.1 m3/s/m (per meter width of wall). With this information and using engineering judgment I conclude that the most probable sequence of multi-hazard cascading failure during this in cident was: wave impact force leading to masonry failure, loss of infill, and failure of the structure following successive tides. The multi-hazard cascading risk model developed in this research is applicable for other infrastructure under a variety of natural hazards. Examples are presented in this research. Given the current global climate emergency and sea level rise, it is expected that the results of this work will provide an important contribution to infrastructure resilience to natural hazards.

The first mammals evolved as small-bodied insectivores in the shadow of the dinosaurs during the Mesozoic, but truly large body sizes and dominance of terrestrial ecosystems were only attained by mammals in the Cenozoic after the end-Cretaceous mass extinction. Yet, the extent and trajectory of mammalian palaeoecological diversity through the Late Cretaceous before the mass extinction and in its immediate aftermath in the early Paleocene remain incompletely understood despite centuries of fossil collecting and study. Recent developments in palaeodietary reconstruction using robust, quantitative proxies provide a timely opportunity to examine these issues. This thesis uses the well-resolved record from North America to test hypotheses related to mammalian dietary palaeoecology through the Late Cretaceous and early Paleocene. Firstly, a new quantitative review of dietary interpretations for Late Cretaceous mammals is presented, which reveals support for a rejection of the traditional Mesozoic 'suppression hypothesis'. However, the quality and consistency of interpretations are variable, highlighting the need for robust palaeodietary work in future. Secondly, a diverse set of extant herbivorous mammals is used to explore the benefits of applying and combining two dietary proxies: multi-proxy dental morphology analysis (MPDMA) and dental microwear texture analysis (DMTA). This study shows for the first time that multivariate metrics from both techniques are significantly but variably correlated and that dietary classification improves by combining both methods. Thirdly, MPDMA and DMTA are then applied to early Paleocene 'condylarths' (so-called 'archaic ungulates') from the San Juan Basin in New Mexico, providing strong support for the rapid recovery and radiation of placental mammals in the aftermath of the mass extinction. Finally, a novel multi-comparator approach to DMTA sheds new light on mammalian responses to an abrupt hyperthermal event in the early Paleocene, which has important implications for assessments of extinction risk amidst the current climate and biodiversity crises facing our planet.

Two sets of lateral spin valves (LSVs) were fabricated - Permalloy (Py)/ Silver (Ag) and Py/ Copper (Cu). Both sets of devices were made with 99.9999 % (six 9s) pure metal, evaporated at a rate that would optimise their crystal structure. However, the deposition of the non-magnetic material in both sets was paused midway, for 25 minutes, before the growth was completed. This was done in order to purposefully introduce ambient impurities from the deposition chamber (such as N2) into the central channel of the devices and, as such, act to disrupt the quality of the crystal structure. Both 'local' and 'non-local' direct current (DC) reversal sweeps (± 500 µA) were performed at a range of temperatures (3 K up to 290 K) and applied magnetic field strengths (± 100 mT), for devices with a variety of injector-detector separations (550 nm to 2650 nm) in order to extract their thermal, electrical and spintronic properties. A model recently presented by Stefanou et al. [1] was applied to the thermal voltages measured in both sets of devices resulting in a detailed insight to the thermal differences between Cu and Ag nanowires. It was found that Cu's relatively larger thermal conductivity resulted in a completely different temperature dependence for thermal voltages measured at temperatures below 50 K. The length dependence of the spin signals in both sets of devices were extracted and fitted with a Valet-Fert model for spin diffusion. Careful analysis showed no correlation between the presence of a characteristic Kondo 'upturn' in the resistivity measurements and the magnitude of a low temperature 'downturn' in the spin diffusion lengths for both the Ag and Cu. The introduction of non-magnetic impurities during deposition and hence the disruption of the crystal structure, appears to have significantly reduced the applicability of the Elliott-Yafet (EY) model for spin-flip scattering when compared to similar devices [2-4]. Additionally, a low temperature deviation from the usual quadratic, nonlocal, current-voltage relationship (NLIV), was shown to be very strongly correlated to the magnitude of thermal voltages, caused by Joule heating in the devices' injectors, measured at their detectors [4-6].

Living systems are defined by their thermodynamic openness, by the fact that energy and matter are able to cross their boundaries. Without this capability to interact with their environment, living systems would be unable to support their life-sustaining functions. As a result of this continual interaction with its environment, the interior processes of a living system is forced to operate far from any equilibrium. Indeed, any system that is in equilibrium internally or with its environment could reasonably be characterised as a dead one. The dynamics of systems that are operating far from equilibrium, however, are far from understood. In this thesis, we build on an existing framework for understanding these dynamics, based in the finite-time analysis of non-autonomous oscillatory processes. This approach is motivated by a key consequence of thermodynamic openness - to introduce time-dependence to the open system. We develop an original mathematical model for the energy metabolism of cells using inter-coupled networks of non-autonomous phase oscillators, with intra-network weighted coupling. The effect of each of this model's components on its dynamics and stability is numerically analysed. Experimental data of the metabolism of HeLa cells is analysed, finding the fundamental frequencies of this process. This analysis is used to demonstrate the capability of the model to reproduce the complex dynamics of the experiment, and this is contrasted to a comparable model of an alternative framework. It is this capacity of non-autonomous oscillations to simply and deterministically produce apparently highly complex dynamics that justifies our application of them to this problem. We demonstrate it further by viewing them through the framework of statistical time-series analysis, finding that even a single non-autonomous oscillator can appear to be 1/fβ noise in a power-spectral density estimation. Autonomous systems are shown to only present as noise when there are many of them, and hence it is the introduction of time-dependence that generates such complexity so readily. We demonstrate that this also occurs for coupled networks of non-autonomous oscillators, and in real experimental data. Analysis tools based in a finite-time framework, however, are shown to detect informative deterministic frequencies and couplings in both the numerical and experimental cases. Overall, this thesis demonstrates that networks of non-autonomous oscillations are physically linked to living systems through the time-dependence introduced by thermodynamic openness. Additionally, it is shown that they are able to reproduce living systems' complex dynamics in a simple and usable way. Finally, it is established that much greater information about such an open system can be gained when they are analysed with this time-dependent deterministic framework in mind.

Jet fuel is used as a coolant for lubricants and oils, and receives heat from the burner feed arm before combustion. The thermal stress received by the fuel, in combination with dissolved oxygen, results in reactions yielding carbonaceous deposits on fuel-wetted surfaces. These deposits can cause efficiency and safety issues as they grow on critical components. The initial stage of the deposition process involves a well understood autoxidation mechanism, leading to a series of well characterized oxidized molecules. However, it is less clear what chemical mechanisms lead to the agglomeration of these oxidized molecules producing deposits. The aim of this thesis is to gain a more fundamental understanding of the agglomeration and deposition process. Density functional theory (DFT) and experimental techniques including gas/liquid chromatography mass spectroscopy (GC/LC-MS) were used to investigate these processes. Additionally, kinetic analysis using pseudo-detailed mechanisms were performed throughout to explore competing pathways. The Soluble Macromolecular Oxidatively Reactive Species (SMORS) mechanism has previously been proposed as a universal mechanism for deposition, but has received little mechanistic scrutiny. Our DFT calculations performed here showed that the originally proposed SMORS mechanism involving electrophilic aromatic substitution (EAS) was kinetically and thermodynamically prohibited. Instead, it was found a homolytic aromatic substitution (HAS) mechanism could allow C-C bonds to form to lead to agglomerated species. Additionally, the SMORS mechanism neglects to elucidate the role of indigenous fuel sulfur compounds, which have a major influence on deposit formation. Using surrogate fuels and deposit characterization with GC/LC-MS, it was shown that the addition of sulfur containing compounds to 5- membered fuel nitrogen heterocycles led to oligomers containing nitrogen-nitrogen compounds. This implied sulfur compounds were able to catalyze the coupling. Indigenous fuel sulfurs were also was shown to play a crucial role in the early stage of deposition. DFT calculations showed that compared to other fuel oxygenated compounds, sulfur acids formed from autoxidation of indigenous sulfurs have the highest adsorption energy on stainless steel surface oxides. Exploring the heterogeneity of stainless steel surface oxides, sulfur acids had a higher adsorption energy on Cr2O3 and carboxylic acids had a higher adsorption energy on Fe2O3. Other oxygenated and indigenous fuel components were found to physisorb at lower adsorbtion energies. Finally, using the mechanistic findings from this thesis, 6 pseudo-detailed kinetic mechanisms were built using DFT calculate barriers, each representing a fuel containing a common antioxidant/heteroatom. The calculated mass of deposit dimer from our mechanisms correlated well with the measured mass of deposit formed from 6 equivalent surrogate fuels. The results here show how DFT can be used to build deposition mechanisms from first principles. The chemical mechanistic findings throughout this whole thesis will help guide future researchers to build new predictive models for deposition from first-principles.

This thesis consists of two parts. The first part constructs entropy regularised variational schemes for a range of evolutionary partial differential equations (PDEs), not necessarily in gradient flow form, with a focus on kinetic models. The second part obtains Freidlin-Wentzell large deviation principles and exit times for a class of reflected McKean-Vlasov stochastic differential equations (SDEs). The theory ofWasserstein gradient flows in the space of probability measures has made enormous progress over the last twenty years. It constitutes a unified and powerful framework in the study of dissipative PDEs, providing the means to prove well-posedness, regularity, stability and quantitative convergence to the equilibrium. The recently developed entropic regularisation technique paves the way for fast and efficient numerical methods for solving these gradient flows. However, many PDEs of interest do not have a gradient flow structure and, a priori, the theory is not applicable. In the first part of the thesis, we develop time-discrete entropy regularised, (one-step and two-step), variational schemes for general classes of non-gradient PDEs. The convergence of the schemes is proved as the time-step and regularisation strength tend to zero. For each scheme we illustrate the breadth of the proposed framework with concrete examples. In the second part of the thesis we study reflected McKean-Vlasov diffusions over a convex, non-bounded domain with self-stabilizing coefficients that do not satisfy the classical Wasserstein Lipschitz condition. For this class of problems we establish existence and uniqueness results and address the propagation of chaos. Our results are of wider interest: without the McKean-Vlasov component they extend reflected SDE theory, and without the reflective term they extend the McKean-Vlasov theory. Using classical tools from the theory of Large Deviations, we prove a Freidlin-Wentzell type Large Deviation Principle for this class of problems. Lastly, under some additional assumptions on the coefficients, we obtain an Eyring-Kramer's law for the exit time from subdomains contained in the interior of the reflecting domain. Our characterization of the rate function for the exit-time distribution is explicit.

Since the 1970s, Brazil's authorities have regarded the country's past as a source of cultural and economic value (Gonçalves 2007; Collins 2015). In the late 2000s, a boom in Brazil's consumer economy served to make smartphones and social media ubiquitous across the country (Spyer 2017). This thesis focuses on how these two phenomena intersect in the city and state of Rio de Janeiro. Drawing on material gathered during fieldwork in 2019 and 2020, it examines how a selection of cultural-historical projects use digital media to explore Rio's past. This thesis argues that, through their exploration of Rio's past, each of these projects shapes how people engage with the city and state and reproduces their space (Lefebvre 1991). This analysis of how digital media intervene in the production of Rio's space contributes to scholarship that explores Rio's urban and cultural history (Sevcenko 2003; Needell 1987; Carvalho 2018). In so doing, it adds to literature exploring how the screens of digital media form an integral and constitutive part of the space of contemporary cities (McQuire 2016; Degen and others 2017). The thesis also contends that the projects it examines all reflect and remake contemporary understandings of how Rio should be in ways that are contingent upon and shaped by the material context(s) from which they emerge, namely, Rio's enduring history of racialised urbanism, its authorities' shifting attitude to the past, and changes in Brazil's approach to cultural funding following its return to democracy in the late 1980s (Sevcenko 2003; Gonçalves 2007; Rich and Vieira 2020). Through analysis of the impact of these factors and from the perspective of a city in the Global South, this thesis dialogues with a growing literature in media studies that examines how the historicity of different forms of technology shapes their affordances (Hu 2015; Crawford 2021). The structure of the thesis moves from Rio's centre towards its suburbs and rural hinterlands to examine the different ways that digital media are used to interrogate the past of these distinct areas. Chapter One focuses on Rio's centre. It examines how the circulation of early photographs of Rio on an Instagram page called rioantigo transforms them into axes of debate about what kind of city Brazil's former capital should be. Chapter Two moves from Rio's centre towards its suburbs. It interrogates how a walking-tour initiative, Rolé Carioca, and a virtual museum, Rio Memórias, use a mixture of digital platforms and in-person events to encourage residents of Rio to reconnect with their city's public spaces. Chapter Three considers how glitches, uneven provision of infrastructure, and deliberate acts of sabotage inform the shape of Passados Presentes, a project which uses digital media to explore the legacy of slavery across Rio state.

Minocycline is a second-generation semi-synthetic tetracycline antibiotic that displays additional immunomodulatory and anti-inflammatory properties. The benefit of these properties has proved to be clinically relevant, however, exact immunoregulatory mechanisms behind minocycline's non-antibiotic effects remain unveiled. In the context of inflammatory bowel disease, data has previously shown that minocycline improves mucosal recovery in colitic mice, an effect related to a potentiation of the innate immune response and enhanced inflammation resolution. Minocycline initially enhanced monocyte recruitment to the intestine, whilst simultaneously increasing the presence of Ly6C- MHCII+ macrophages. In vitro, minocycline was shown to both increase and decrease proinflammatory cytokine release which was crucially seen to be time-dependant. Whether these effects derived from a direct action of minocycline on macrophages or other mechanisms is unclear. Macrophages are essential in the regulation of inflammation and resolution and can switch between M1/pro-inflammatory and M2/anti inflammatory phenotypes, with disturbances in M1/M2 homeostasis contributing to the development and maintenance of chronic inflammation. An improved understanding of minocycline's immunoregulatory activity is key for future translational studies into human disease, thus the aim of this research was to evaluate the direct effects of minocycline on monocyte-macrophage differentiation, polarisation, and activation. Three in vitro models were employed: THP-1, U-937 and human PBMCs. When differentiated in the presence of minocycline (10-50μM) with PMA (80nM) for 48hr, minocycline interrupted cellular adhesion and significantly decreased the expression of CD14 and CD86, while increasing the percentage of CD163⁺ cells - an M2 associated marker. When administered to M0 macrophages polarised for 24hr to M1 (20ng/mL IFN-γ+10ng/mL LPS), or M2 (20ng/mL IL-4), minocycline significantly reduced the production of pro-inflammatory cytokines IL-1β, IL-6 and TNF α, while in the M2 exclusively, reduced the expression of CD206 and IL-10, but increased IFN-γ and IL-12p70 production. The transcription factors stat2, 3 and 6 were also reduced by minocycline following M1 polarization. Conversely, when assessing the role of minocycline upon LPS-activated macrophages (100ng/mL for 24hr), minocycline-treated M1 PBMC derived macrophages displayed maintained decreased production of IL-1β but increased TNF-α, IL-6 and IFN-y, with activated M2 macrophages also increasing and decreasing IL-12p70 and IL-10 respectively. This data has highlighted some key regulatory effects of minocycline regarding macrophage biology and have added to the collective knowledge on minocycline's' immunomodulatory effects that can help provide more detailed context to the anti-inflammatory effects seen in vivo. Consequently, this advancement in knowledge will ultimately aid the development of novel therapeutic strategies for those individuals that are burdened with diseases dominated by a dysregulated immune response as seen in IBD.

The posterior endoderm in Drosophila embryos undergoes an epithelial-mesenchymal transition (EMT), driving the collective migration of endoderm cells. This EMT shows many similarities with the so-called 'partial-EMTs' that have been described in facilitating cancer metastasis. A single GATA-binding transcription factor, serpent (srp), is responsible for driving the entire process of EMT in the posterior endoderm. srp was previously shown to directly repress transcription of the key apical-basal polarity regulator crumbs (Crb). However, many changes other than loss of apical-basal polarity also occur during EMT, therefore in my project I aimed to understand how srp activates these cell changes. To explore which other genes srp may be regulating to drive EMT, I used Targeted DNA adenine methyltransferase identification (TaDa). This technique yielded a list of 1,177 genes directly bound by srp, of which 200 were related to mediating the response to ecdysone (20E), the major steroid hormone in Drosophila. To investigate this, I perturbed ecdysone signalling using two separate methods, which both prevented EMT in the posterior endoderm. This lack of EMT was attributed to the improper endocytic recycling of apical-basal polarity regulating proteins and adherens junction components. To test this theory further, I exposed embryos to exogenous sources of 20E, which recapitulated phenotypes observed during EMT at far earlier stages of embryogenesis than is normal. Together, these experiments strongly support a novel role for the co-regulation of srp and 20E in driving the precisely timed changes required for EMT. The characterisation of developmental EMTs provides an understanding of the underlying molecular mechanisms of how EMTs normally occur during tissue morphogenesis. With the finding that activation of EMT in primary tumours can lead to cancer dissemination and metastasis, these findings may aid in the generation of improved therapeutics for metastatic cancer. To test for conserved mechanisms of developmental EMTs in disease using Drosophila, fly models first needed to be generated that accurately recapitulate aspects of human metastasis. I aided in the generation of a Drosophila model for colorectal cancer (CRC) metastasis, that recapitulates many hallmarks of human metastatic CRC. A pilot screen using this model identified 3 compounds with anti-EMT properties, capable of blocking the dissemination of circulating tumour cells. In the future, this model has the potential to be used to investigate and compare mechanisms of developmental EMTs with those involved in cancer metastasis, in particular if steroid hormones play a role in co-activating the process during disease progression.

The thesis re-evaluates Bataille's base materialism via four interconnected and highly original approaches to a 'debased metaphysics' of thought and being's movement. Chapter One shows how this logic has an impact on the way the morphic operates, with implications that form the instant as an autonomous, auto-generative body within a continuous process of being. This atemporality creates a continuous body where the body's continuous aspect establishes both an atemporal instant and eternal version of time. Chapter Two develops how the instantaneous aspect of the body's shape emerges from a generative principle of erotic movement, and is experienced as system, namely atheology, whereas its perpetual or continuous aspect is this system's collapse, which conditions its prior determinacy as form. As will be shown, this dynamic enables new forms of difference to occur which are not relative, the strategic importance of which are developed in Chapter Three. This shows how determinacy/collapse are incorporated into the movement of a body in relation to its parts. Embodied atheology's gestural poiesis is substitution of a system's part for its determined whole, empowering the body part as an acephalic operator. This uncovers the purpose of difference's autonomy, which instead of emphasising general ontological non-meaning, achieves a new type of total metaphysical definition that is exchangeable for the inessentiality of the autonomous body part. Substitution's dynamic means the systematic body auto-invaginates and leaves definition's articulation to the autonomy of the vagina itself. The authority required to determine being has produced autonomy as an ancillary part of this determinacy. Additionally, authority required to determine being also expiates itself. Chapter Four shows how this works by bringing in acephalia as a meditative and shamanic strategy for alteration within being, excusing the obligation of material thought to behave in a materially determined way by making the link between excretion as an expiatory practice, and an eroticised way of being wholly other, either as sound, or animal alteration. The thesis sets up the continuous body as a new conception of being, a system of being, its practice, and a more radical notion of expiation as shape-shifting as ontic transfer, that, put together, locates an ensembled context for a debased metaphysical shamanic anarchism.

First-year medical students Learning and Teaching Resources (LETERs) include a considerable amount of discipline-specific vocabulary for English for Medical Purposes (EMP) such as the technical and the sub-technical. The former refers to the specialised vocabulary used only in a specific field (Chung and Nation, 2004, Coxhead, 2013), while the latter refers to the shared vocabulary amongst academic disciplines (Baker, 1988; Hsu, 2013). First year medical students' familiarization with the technical and sub-technical vocabulary typically occurs from reading LETERs during their coursework and was cited as a contributing factor towards their study-related stress and burnout (Sinclair, 1997; Boni et al., 2018). The density of Learning and Teaching Resources (LETERs) as part of first year medical students' coursework in terms of technical and sub-technical vocabulary as well as the receptive and productive vocabulary of L1 and L2 medical students in their first year is an area that has been unexplored by scholars in the field of EMP. Thus, the aim of this study is to look into the technical and sub-technical vocabulary of medicine from multiple perspectives such as its density in medical texts and examine the recognition and production of technical and sub-technical vocabulary from a total sample of 115 (L1 and L2) first year medical students in the UK. In order to collect the language data, two corpora of medical language were compiled as part of this study: the Medical Receptive (MEDREC) corpus of 2,097,627 running words based on 6 types of LETERs and the Medical Productive (MEDPRO) corpus of 209,160 running words of115 written samples. Findings from lexical density analysis on LETERs suggests a propensity towards a higher degree of usage of technical vocabulary and results from the Receptive Recognition (RecRec) Task indicate a significant progress by the end of the initial semester in both technical and sub-technical vocabulary. In addition, analysis of productive vocabulary usage suggests that the sub-technical vocabulary was denser in medical students' writings, which is inversely proportional in relation to the vocabulary that medical students were introduced to from LETERs texts with L1 or L2 English having a minimal effect on findings. The original contribution of this thesis is to fill a gap in the current literature on the complexity of disciplinary vocabulary used in LETERs and the development of the RecRec Task suitable for new medical/EMP students. In addition, it is one of the first experimental studies in medical English, which involved both L1 and L2 medical students' receptive and productive vocabulary skills.

Autistic individuals are at disproportionately high risk of experiencing mental health issues, and the quality and accessibility of mental health care are reduced in this population. Investigating the impact of using digital technology in mental health research, assessment, treatment, and care for autistic individuals (i.e. digital mental health, DMH) may help to reduce this disparity. This is suggested because of its apparent potential in aiding adaptations that are recommended for autistic individuals to reduce autism-associated complexities in these domains, but equally because it may introduce challenges which are important to identify given the increasing popularity of DMH. The recommended adaptations that digital technology may aid in these domains include the use of individualised and multi-modal approaches. This thesis thus aims to explore DMH for autistic individuals, specifically directly for autistic individuals themselves, rather than solely for or via parents/supporters. Objectives include identifying its potential feasibility and acceptability, alongside challenges, benefits, facilitators, and other considerations. Section A focuses on DMH targeting anxiety and commences with a systematic review which indicates it to be broadly feasible and acceptable except when involving social scripts or peer modelling. The review further highlights research gaps that include the use of (1) virtual reality (VR) exposure therapy for social anxiety (SA) disorder and (2) of remote interventions in general. The first research gap is explored in subsequent chapters that present the process of developing an intervention study with young people, their parents, and therapists. Key considerations identified include introducing VR carefully and ensuring sufficient individualisation. Candidate VR exposure tasks identified surround approaching and conversing with others, experiencing perceived injustice, being the centre of attention, and situations involving novelty and/or lower predictability. The second research gap is explored in Section B which focuses on the use of telepsychiatry interventions during the pandemic. It commences with a service evaluation of a local trust via the thematic analysis of semi-structured interviews with therapists and young people regarding their experiences. A research study is then presented that involves a mixed methods web-based survey examining clinicians' views. Findings broadly indicate that remote delivery was challenging, but overall levels of concern were low, and some service-users favoured it or hybrid delivery. Patterns in findings are also observed across thesis studies. Individual characteristics considered to render the DMH intervention unviable include attention deficit hyperactivity disorder (ADHD) and intellectual disabilities, but some considered the reverse to be true with respect to such characteristics. Perceived challenges principally surrounded the variability in acceptability, minimal evidence-base, and certain autism-associated difficulties considered to reduce its accessibility such as social avoidance. Perceived benefits surround digital technology holding potential in facilitating the control and monitoring of stimuli and in enhancing the treatment accessibility for certain individuals. Individuals in late adolescence who find in-person interactions difficult, require minimal support, and show technological affinities, are amongst those considered most likely to benefit from DMH interventions. Thesis findings preliminarily indicate that DMH for autistic individuals broadly shows promise and provide a plethora of considerations and avenues to guide future work and clinical implementation.

BACKGROUND: The onset of COVID-19 brought significant change to the structure and delivery of mental health services. As such, the need for a clear evidence base and understanding of remote interventions for mental health difficulties such as psychological trauma are of utmost importance. The examination of interventions has generally lacked in quality and scope. Moreover, this evidence has rarely accounted for the experiences of those involved in the delivery of interventions. METHOD: To this end, the current portfolio utilises two research methods to examine this phenomenon. Firstly, a systematic review of quantitative papers assessed the efficacy, feasibility, and overall study quality of one-to-one remote interventions for psychological trauma. Findings were presenting using a narrative synthesis of 15 empirical papers. Secondly, an empirical paper employed a predominantly qualitative mixed-methods design to explore individual lived experiences of clinicians utilising trauma interventions remotely throughout COVID-19. A background questionnaires as well as individual interviews were used, whilst Interpretative Phenomenological Analysis (IPA) was applied to explore the lived experiences of clinicians specific to the recent context of working with psychological trauma remotely. RESULTS: The systematic review indicated good efficacy for a variety of manualised treatments for psychological trauma delivered remotely. In addition, such findings were found to be comparable to traditional, face-to-face conditions. Efficacy was supported by large effect sizes, as well as feasibility in relation to client satisfaction and clinician fidelity in particular. However, there was an overall limited quality of included studies, with specific issues found relating to uptake, attrition and controlling for confounders. Results of the empirical paper reported changes to caseloads and perceived ability of different forms of delivery, as well as yielding four superordinate themes: 'Progressing the trauma treatment journey', Building a Therapeutic Relationship Remotely', 'Learning over time', and 'Creating change in how we work'. CONCLUSIONS: Findings from the review contribute to the evidence base for clinicians actively engaged in remote interventions for psychological trauma. However, the lack of quality and predominant account of short-term, Type 1 trauma limits the generalisability to other trauma populations and presentations. Key markers for methodological quality are noted for future researchers, whilst also highlighting the need for both qualitative methods and grey literature. Qualitative findings suggest clinicians can experience both opportunities and challenges when working with trauma remotely, which is impact at both a client and service level. The use of clinicians' accounts provides direct implications to inform services providers in how clinicians may adapt interventions according to the nuances of remote working.

Hypertension is a prevalent condition with clear links to increased mortality and morbidity. The sympathetic nervous system is a key regulator of blood pressure and sex differences in sympathetic blood pressure regulation may contribute to the reduced hypertension prevalence in premenopausal women compared to young men. However, hypertension in premenopausal women exists and the underlying mechanisms are poorly understood. Furthermore, whilst female hypertension risk is greater after the menopause, the mechanisms promoting hypertension in some postmenopausal women but not others remain unclear. This thesis hypothesised that hypertensive women exhibit altered sympathetic regulation versus normotensive controls. Firstly, the transduction of sympathetic nerve activity into blood pressure was measured in hypertensive and normotensive pre- and postmenopausal women (and equivalent male groups), using an established method. Transduction was increased in hypertensive versus normotensive premenopausal, but not postmenopausal women. Additionally, sympathetic transduction was negatively associated with age in hypertensive women. These data indicate a role for increased sympathetic transduction in hypertensive premenopausal but not postmenopausal women. The hypothesised mechanism driving increased sympathetic transduction in hypertensive premenopausal women (poorer beta-adrenergic receptor function versus normotensive controls), was investigated, but data collection was difficult (due to the COVID-19 pandemic), and this question remains unanswered. Additionally, the thesis aimed to determine whether respiratory modulation of sympathetic activity was altered in postmenopausal versus premenopausal women, given that age does not appear to affect respiratory sympathetic modulation in men. The data showed that respiratory sympathetic modulation is reduced in healthy postmenopausal women compared to younger adults, but that hypertension had no additional effect. As such, poorer respiratory modulation may be a mechanism by which ageing is associated with increased sympathetic activity in women. Overall, these data have contributed to the understanding of two aspects of sympathetic blood pressure regulation in women, with important implications for the understanding of hypertension development in women.

In Hirst v United Kingdom (No.2) (Hirst) the European Court of Human Rights (ECtHR) held that the UK's legislative ban on prisoner voting violated Article 3 of Protocol 1 of the European Convention on Human Rights. Following Hirst, a protracted constitutional clash between the UK and Strasbourg ensued, as the UK resolutely resisted compliance with the judgment in Hirst. The UK Government introduced administrative amendments which appear to have resolved the clash. However, this thesis argues that these amendments fundamentally undermine the ECtHR's requirements for legislative amendments, as the Committee of Ministers of the Council of Europe sanctioned a form of corrective compliance. This thesis unravels the constitutional controversy of prisoner voting, which enables detailed understanding of the multifaceted nature of inter-institutional roles and relationships in rights protection. In exploring the clash, first to situate the discussion, this thesis delineates the background context to prisoner voting. It then explores the key principles relevant to rights protection in the UK and at the European level. The core of this thesis provides a detailed analysis of the approaches of the domestic courts, European courts and political institutions to prisoners' voting rights. Crucially, rather than attributing blame to any one institutional actor, this thesis argues that the clash reveals multiple institutional failures in terms of rights protection. As such, it is proposed that the clash constitutes a "lose-lose-lose-lose-lose" scenario. It is a "loss" to the domestic courts, as their generally hands-off approach to prisoners' voting rights undermined human rights protection, revealing judicial reticence regarding the exercise of the constitutional role accorded to them under the Human Rights Act 1998 (HRA), which contributed to their failure to hold the UK Government to account. It is a "loss" for Parliamentary protection of rights as Parliament's involvement was circumvented and the clash has seemingly been resolved by executive administrative amendments. Further, it constitutes a "loss" for the Government, as its resolution of the clash was only reached after several years of prolonged conflict in which it sustained repeated criticism for its recalcitrant response to prisoner voting, resulting in reputational damage. It is a "loss" for the ECtHR, as its jurisprudence and its legitimacy were undermined by the UK's non-compliance and its loss was then solidified by the CM's endorsement of the UK's administrative amendments which undermined the ECtHR's requirement for legislative change. The CM's acceptance of the UK's administrative amendments also constitutes a loss to the authority of Strasbourg's political institutions. In assessing why each institution lost, this thesis argues that the domestic courts' reticence was primarily evident in their decision to refrain from granting a second declaration under s.4 HRA. The domestic courts were excessively deferential to the political branches as they were overly concerned with the expected negative political responses to the declaration. Instead, it is argued that the Supreme Court in Chester in particular, should have recognised the declaratory nature of s.4 HRA, that it respects and allows for political discretion. The Court's non-interventionist approach accorded the political branches greater leeway to procrastinate and opt for minimalist compliance. Therefore, the Court should have granted a second declaration to reiterate the incompatibility. Further, whilst the Joint Committee on Human Rights had a valuable role in monitoring the Government's compliance, ultimately Parliament failed to take an active role in the issue of prisoner voting. This accorded the Government greater scope to resist compliance. Moreover, the main cause of the ECtHR's loss is the lack of clarity and consistency of the ECtHR's case-law which undermined its procedural legitimacy. This further enabled the Government to resist Hirst. Therefore, a clearer and more consistent approach would have ameliorated the ECtHR's loss. The CM's loss was crystallised by its acceptance of the UK's administrative amendments and in doing so, it also undermined the ECtHR's case-law. The CM should have remained robust that legislative amendments were required to ensure compliance with Hirst. The analysis of these multi-dimensional institutional losses shows the institutional tensions that exist within and between institutions in navigating their roles in terms of upholding rights. When rights protection is placed under pressure by conflict, this can reveal challenges and weaknesses in the mechanisms of rights protection. Whilst ideally institutions should work collaboratively to ensure that rights are upheld, this can jar with the conflict-ridden reality of rights protection which may lead to rights being undermined. This analysis therefore extends understanding of the reasons why the prisoner voting clash specifically resulted in major challenges, and this thesis also considers what this shows about the roles and relationships of the key institutions discussed in rights protection. Crucially, this thesis argues that prisoner voting reveals that the institutional losses were mutually reinforcing and contributed together to rights protection being undermined. Therefore, blame cannot be solely attributed to one institution. Rather, each loss contributed to other losses. This thesis considers the broader lessons that can be learnt from the clash to attenuate or avoid such losses from occurring in the future. It concludes that the lesson of the prisoner voting rights controversy is that multi-institutional robustness is required to ensure effective compliance and that rights are upheld. For instance, this thesis argues that: domestic courts should confidently exercise their powers and grant a declaration of incompatibility under s.4 HRA; the UK Parliament should have greater oversight of the executive's role in human rights issues at the supranational level; Strasbourg's institutions should further enhance domestic parliament's involvement; the ECtHR's judgments should be as clear and as consistent as possible to increase its procedural legitimacy; and there should be institutional cohesion between CM and the ECtHR, meaning that the CM should refrain from sanctioning amendments which would fundamentally override, undermine or contradict the ECtHR's judgment. Reinforcing institutional robustness and emphasising the combined institutional effort required to uphold rights could therefore operate to enhance rights protection, increasing the likelihood of effective compliance.

Pluripotent stem cells are characterized by their capacity for self-renewal and differentiation, playing a critical role in the maintenance and regeneration of tissues. The composition, organization, and topology of the extracellular matrix (ECM) within the tissue microenvironment, collectively known as the niche regulates stem cell fate. Integrins are heterodimeric receptors that interact with extracellular matrix proteins, forming a mechanical link between the ECM and the actin cytoskeleton. The dimensionality, chemistry, topography, and elasticity of the microenvironment can be tuned to modulate gene expression and stem cell fate. These force-induced changes in gene expression and stem cell fate are mediated by dynamic regulation of signalling, adaptor and cytoskeletal proteins, nuclear morphology and chromatin organization in response to mechanical stress. This study aimed to characterise the integrin heterodimers and integrin-dependent signalling networks recruited on the ECM ligands vitronectin and fibronectin, and two self-assembling nano engineered polymers that serve as stem cell substrates that promote self-renewal, ZTFN and ZT910 Immunofluorescence imaging demonstrated that iPSCs plated on vitronectin fibronectin, ZTFN and ZT910 recruited αVβ5, α5β1, αVβ1 and α5β1 respectively to integrin-associated adhesion complexes. The distinct integrin heterodimers recruited on vitronectin, fibronectin, ZTFN and ZT910 were confirmed using adhesion complex enrichment and integrin inhibition assays. Traction force microscopy of iPSCs plated on hydrogels of different rigidities (5kPa to 70-100 kPa) demonstrated that vitronectin fibronectin, ZTFN and ZT910 induced differential force transmission on soft and stiff, but not intermediate rigidity matrices. Suggesting that the different integrin heterodimers possess distinct biophysical properties that are tuneable in a rigidity-dependent manner. To determine how the mechanical properties of different integrin heterodimers influence stem cell behaviour, nuclear morphology, chromatin organisation and YAP localisation, iPSCs were plated on substrate-coated hydrogels of different rigidities. Under these conditions, iPSCs demonstrated no difference in nuclear morphology or YAP localisation but exhibited significant changes in substrate and rigidity dependent chromatin organisation suggesting that distinct biophysical properties integrin dependent gene regulation. Adhesion complex enrichment was employed to isolate and characterise for the first-time integrin adhesion complexes recruited by iPSC on vitronectin, fibronectin, ZTFN and ZT910. The αVβ5-VIT, α5β1-FN, αVβ1-ZTFN and α5β1-ZT910 adhesomes exhibited broad convergence when comparing the α5-mediated adhesomes (fibronectin and ZT910) and αV mediated adhesomes (vitronectin and ZTFN). Bioinformatic analysis of α5β1-IACs and αVβ5- IACs recruited on fibronectin and vitronectin respectively revealed enrichment of gene ontology terms containing Focal Adhesion and Metabolism proteins. Integrative analysis revealed that SLC3A2 may play a potential role in regulating both integrin mechanosignalling and metabolism. Immunofluorescence imaging demonstrated that SLC3A2 localises to α5- mediated adhesions, but not αV-mediated adhesions, suggesting that SLC3A2 may modulate mechanosignalling and metabolism in an α5β1-heterodimer specific manner. Traction force microscopy revealed that SLC3A2 knockdown did not affect force transmission of iPSCs plated on vitronectin or fibronectin. However, treatment of iPSCs with SLC3A2 siRNA alone or in combination SLC3A2 light chain inhibitor LAT1 significantly reduced overall intracellular ATP 3 levels, demonstrating a putative impact on cellular energetics and metabolism. Analysis of the SLC3A2-LAT1 cryo-EM structure enabled the identification of SLC3A2-LAT1 regulatory domains and constructs were generated to target different structural domains of the SLC3A2- LAT1 complex. These constructs will allow dissection of the relative contribution of SLC3A2- integrin-binding to SLC3A2-LAT1-mediated amino acid transport, in force transduction, metabolic reprogramming and transcriptional regulation. Together, these advances contribute to our understanding of the mechanisms by which integrin-ECM engagement regulates global cellular processes in stem cells but will likely also have relevance in somatic cell biology and disease.

Physical activity that includes elevation or speed, such as cycling, carries the risk of head injury. The risk of injury is mitigated by wearing safety helmets. Whilst cycling is adopted as an exemplar when evaluating new helmets, garnering notable research interest in recent years, head injury remains a notable cause of mortality and morbidity in cycling accidents. Indeed, head injury still causes 69-93% of fatal bicycle accidents; hence, new helmet technologies have significant social importance. A critical strategy in head injury mitigation in cycling accidents is the use of a protective helmet and is strongly advocated by The World Health Organisation. It has been reported that the likelihood of sustaining a traumatic brain injury (TBI) is reduced (18%) when wearing a helmet compared to non-helmet cyclists (48%). Current bicycle helmets are designed to protect the user by deforming to mitigate the impact energy and reduce the resultant acceleration. Due to the onset of permanent deformation within the helmet following an impact, its protective capacity is diminished. Consequently, they do not provide adequate performance when subject to a history of loading, such as multiple or consecutive impacts. Indeed, it is common to wear a previously damaged helmet despite contrary advice. Current multi-hit solutions are derived from elastomeric foams which have been applied in several other sporting helmets. These materials, however, suffer from a lack of development in recent years. Furthermore, they have limited geometric freedom, which precludes optimisation. This thesis describes four related investigations which present a finite-element based optimisation approach to the development of new helmet liners leveraging the mechanical benefits of cellular structures and elastomeric materials realised through additive manufacturing. A laser sintered elastomer was characterised by performing low, intermediate and high rate uniaxial tension tests manufactured under three build orientations. Furthermore, planar, equibiaxial tension and stress relaxation tests were carried out. These data demonstrated notable anisotropy, as well as significantly different behaviour across strain rates and deformation modes, necessitating fit of an augmented hyperelastic and linear viscoelastic model. FE software was then used to calibrate material model coefficients, with their validity evaluated by comparing the simulated and experimental behaviour of the material in isolated (uniaxial tensile) and mixed modal (honeycomb compression) deformation states. Close correlation demonstrated that the material model coefficients were valid, removing a barrier to adopting exclusive finite-element based in future investigations. Further, laser sintering was used to manufacture different structural variations of a novel pre-buckled circular honeycomb. The mechanical behaviour of these structures was examined under both quasi-static and dynamic impact loading. Pre-buckled circular honeycombs with aspect ratios, defined as the ratio of minor to major axis of the honeycomb elliptical profile, e = 0.8 and e = 0.6 were compared to a traditional, straight-walled honeycomb, e = 1.0. It was found that the mechanical behaviour of the honeycomb can be tailored to yield different mechanical responses. Principally, decreasing the aspect ratio reduced the stress at yield, as well as the total energy absorbed until densification, however, this alleviated the characteristic stress-softening response of traditional honeycombs under static and impact conditions. When subjected to multiple cycles of loading, a stabilised response was observed. Finite element simulation closely agreed with the experimental results. A simplified, periodic boundary condition model was also investigated, which closely represented the experimental results whilst alleviating computational run time by nominally 75%. The numerical full factorial parameter design sweep identified a broad range of mechanical behaviour, enabling identification of geometric bounds to be used in future optimisation studies. Finite element simulation was used to analyse the response of an elastomeric prebuckled honeycomb structure under impact loading, to establish its suitability for use in helmet liners. Finite element-based optimisation was performed using a search algorithm that uses a radial basis function. This approach identified optimal configurations of the pre-buckled honeycomb structure, based on structural bounds identified from previous investigations, subject to impact loading conditions. Furthermore, the influence of objective function, peak acceleration and head injury criterion was analysed with respect to the resultant mechanical behaviour of the structure. Numerical results demonstrate that this class of structure can exceed the performance threshold of a common helmet design standard and minimise the resultant injury index. Experimental testing, facilitated through laser sintering, validated the output of the numerical optimisation. When subject to initial impact loading, the fabricated samples satisfied their objective functions. Successive impact loading was performed to assess the performance and degradation. Samples optimised for peak acceleration demonstrated superior performance after stabilisation, relative to their initial response. The finite-element based optimisation sequence was repeated using boundary conditions (contact area, mass and velocity) associated with the helmet design envelope and standard. Two optimal configurations, based on different objective functions, peak translational acceleration and head injury criterion, were then proliferated throughout a helmet liner before being subjected to typical frontal head impacts under direct and oblique conditions. Comparison was drawn relative to two densities of a common multi-hit material used in helmet liners, vinyl nitrile foam. Kinematic-based injury criteria were calculated, as well as tissue-based injury criteria, using a validated finite element model of the human head for each impact. Results demonstrated that the optimal pre-buckled honeycomb liners had the best performance, yielding reductions in both kinematic and tissue-based injury criteria. Under direct impacts, values for head injury criterion, maximum principal strain and cumulative strain damage measure were reduced by 34%, 8.6% and 23.7%. Under oblique impact, values for head injury criterion, rotational injury criterion, generalized model for brain injury threshold, head impact power, maximum principal strain and cumulative strain damage measure were reduced by 49.9%, 56%, 29.6%, 40.8%, 14.9% and 66.7%. Honeycombs optimised using head injury criteria as the objective function yielded a reduction in all severity metrics relative to honeycombs optimised using peak translational acceleration, though design standards mandate an acceptable threshold for peak translational acceleration yet not for other injury metrics. The work reported in this thesis identifies a successful design and optimisation strategy to aid and inform the development of next generation helmet liners.

Stimuli presented as pictures are recognised better than those presented as words (Paivio, Rogers, & Smythe, 1968; Shepard, 1967). Numerous theoretical accounts have been proposed to explain this robust Picture Superiority Effect (PSE), though inconsistent evidence has made it difficult for researchers to agree on any one explanation (Mintzer & Snodgrass, 1999; D. L. Nelson, Reed, & Walling, 1976; Paivio, 1971). These inconsistencies are likely attributable to methodological differences and a lack of specificity across studies (Koen & Yonelinas, 2014; Migo, Mayes, & Montaldi, 2012; Schoemaker, Gauthier, & Pruessner, 2014), with various stimulus formats being used to represent a "picture" (e.g. line drawings/shaded illustrations/photographs) and a range of available response options when categorising recognition memory judgements. This thesis reports six experiments in which stimulus format and response option condition were systematically examined in an effort to characterise the relative contribution of different types of picture on successful recognition. Standard PSE response patterns were initially established using words and greyscale drawings in a modified RK paradigm (Experiment 1), before a new set of photograph object stimuli were curated in order to depict the same concepts across numerous formats (Experiment 2). Subsequent recognition experiments were the first to identify a Photograph Superiority Effect (PhSE), whereby photographs produced significantly better recognition than drawings and words (Experiment 3). This effect emerged in both greyscale and colour stimuli, though colour information in itself did not further enhance performance (Experiment 4). The PhSE was robust to further methodological manipulations, such as increasing the distinctiveness of word stimuli (Experiment 5) and providing written-word labels alongside photographs (Experiment 6). Findings are discussed in relation to two major accounts of picture superiority: perceptual distinctiveness (Mintzer & Snodgrass, 1999; D. L. Nelson et al., 1976) and Dual-coding Theory (Paivio, 1971).

Organizational functions and processes have been historically separated into specializations requiring specialized knowledge, skills, and responsibilities. However, very rarely is a process performed entirely by one person or department in the organization. Highly likely, a process is conducted, or requires the assistance of another person or group of persons, or even another department, and whose members may have their own structures, schedules, and schemes of pursuing a particular task. While this configuration has lasted for a long time, and may have its advantages, it has been argued that it leads to inefficiencies, and creates an environment in which individuals feel constrained and believe that their primary goals are to complete their stated responsibilities (Bennis and O'Toole, 2005). But, as modern supply chains become exposed to various interruptions, managers believe that a cross-functional orientation could help companies to discern and mitigate such interruptions. This study utilizes the features of goal interdependence to investigate the cross-functional relationships between two of the primary business functions, namely operations, and financial management, with particular reference to supply chain management and working capital policy, in a metalworking and maintenance, repair, and operations (MRO) products and services firm in the United States. The study uses an explanatory sequential mixed methods design (Creswell, 2017), grounded in the action research methodology. Quantitative data were collected through closedended questionnaire, and analyzed using correlation analysis. Subsequently, qualitative data were collected through observations and semi-structured interviews, and analyzed using thematic analysis and Cronbach's Alpha. The findings of the study indicate that despite an understanding that supply chain and working capital management are essential functions for company success, human attitudes seemed to impede the coordination of the processes between the two functions, and were influenced by a lack of knowledge sharing and unwillingness to collaborate. The intervention revealed that individuals were more willing to work together if they knew the practical complementarity between the functions.

British red squirrels (Sciurus vulgaris) are listed as endangered on the IUCN Red List due to the invasive grey squirrel (Sciurus carolinensis), introduced to the UK in 1876 which outcompete red squirrels for resources. Grey squirrels also carry squirrel poxvirus (SPQV), harmless to the hosts but fatal to red squirrels and the cause of localised extinction. Urgent conservation efforts, including captive breeding and release programmes, are required to prevent extinction of the wild population by 2040. However, stereotypical pacing is prolific in the captive population, starting post weaning and often continuing into adulthood, and although it is recognised as a sign of poor welfare little is understood as to why it occurs. The aim of this study is to observe the onset of stereotypical behaviour in captive individuals and how this behaviour develops over time, through different seasons and in different environments and to use keeper replies to a behavioural survey on the wider British captive red squirrel population to compare and corroborate observed data to determine the major predictors and possible aetiology of stereotypical behaviour in post-weaned, captive red squirrels. Two studies comprise this research project. The first, involved 500 hours of observations of the breeding enclosure and walkthroughs at Wildwood Escot (Devon) and Wildwood Kent captive red squirrels (n=16) over 18 months. The results showed significant differences between wild red squirrels and pacing red squirrels' behaviour (p≤0.001) and a strong negative correlation (r=-0.6) between feeding and stereotypical behaviour. There was also an absolute difference in the presentation of stereotypical behaviour before and after alterations to the breeding enclosure (addition of privacy boards, leaf pile substrate and hoarding containers). Study two involved sending a survey to eight zoos involved in captive breeding programmes, analysis of these completed surveys showed that stereotypical pacing is linked with dispersal needs in post weaned juveniles and foraging and hoarding stress in older squirrels. In conclusion, moving juveniles between 10-14 weeks old, increasing hoarding potential, offering seasonal diets, increasing enclosure complexity, and providing cover could potentially reduce stereotypical behaviour in captive red squirrels and improve welfare.

The highly-conserved exocyst complex plays key roles in vesicle transport and establishment of polarity. It predominantly localises to sites of active cell growth. However, there is emerging evidence that the exocyst functions in other cellular contexts. The exocyst serves several functions at primary cilia, which culminate in a strong association between genetic mutations in the exocyst and ciliopathies. However, whilst we know it localises to these structures and performs essential roles, the specific mechanisms by which it contributes to ciliogenesis and ciliary function remain unknown. I hypothesised that the exocyst's contribution to ciliogenesis extended beyond its role in vesicle trafficking. Here, I use a combination of molecular, cell biology and biochemistry techniques to show that the exocyst is required for ciliogenesis via both the vesicle-dependent and independent routes. I recapitulated two ciliopathy-associated exocyst mutations, EXOC4 p.Q578R and EXOC8 p.E265G, and demonstrate that these are detrimental to the exocyst's functions in ciliogenesis. In addition, I report novel roles for the exocyst at the nuclear envelope that contribute to ciliogenesis. I show that exocyst subunits localise to the inner face of the nuclear envelope, as well as throughout the nuclear matrix. Here, they are required to mediate the composition of both the nuclear lamina and transmembrane proteins in the nuclear envelope, with (likely) consequential effects for both nuclear morphology and chromatin architecture. As functional links have recently been established between the nuclear envelope and ciliogenesis, I examined whether the roles of the exocyst at these sites were also linked. I report that lamin levels are also altered in other ciliopathy models, and that reduced lamin expression is upstream of the ciliogenesis defect in exocyst-depleted cells. In conclusion, this thesis provides an attractive model to inform future studies, whereby ciliopathy proteins around the nuclear periphery come together to control nuclear envelope composition and lamina organisation, with potential consequences for a plethora of cellular processes.

Wheat is one of the most important crops globally with 776.4 million tonnes produced in 2019 alone. However, 10% of all wheat yield is predicted to be lost to Septoria Tritici Blotch (STB) caused by Zymoseptoria tritici (Z. tritici). Throughout Europe farmers spend £0.9 billion annually on preventative fungicide regimes to protect wheat against Z. tritici. A preventative fungicide regime is used as Z. tritici has a 9-16 day asymptomatic latent phase which makes it difficult to detect before symptoms develop, after which point fungicide intervention is ineffective. In the second chapter of my thesis I use hyperspectral sensing and imaging techniques, analysed with machine learning to detect and predict symptomatic Z. tritici infection in winter wheat, in UK based field trials, with high accuracy. This has the potential to improve detection and monitoring of symptomatic Z. tritici infection and could facilitate precision agriculture methods, to use in the subsequent growing season, that optimise fungicide use and increase yield. In the third chapter of my thesis, I develop a multispectral imaging system which can detect and utilise none visible shifts in plant leaf reflectance to distinguish plants based on the nitrogen source applied. Currently, plants are treated with nitrogen sources to increase growth and yield, the most common being calcium ammonium nitrate. However, some nitrogen sources are used in illicit activities. Ammonium nitrate is used in explosive manufacture and ammonium sulphate in the cultivation and extraction of the narcotic cocaine from Erythroxylum spp. In my third chapter I show that hyperspectral sensing, multispectral imaging, and machine learning image analysis can be used to visualise and differentiate plants exposed to different nefarious nitrogen sources. Metabolomic analysis of leaves from plants exposed to different nitrogen sources reveals shifts in colourful metabolites that may contribute to altered reflectance signatures. This suggests that different nitrogen feeding regimes alter plant secondary metabolism leading to changes in plant leaf reflectance detectable via machine learning of multispectral data but not the naked eye. These results could facilitate the development of technologies to monitor illegal activities involving various nitrogen sources and further inform nitrogen application requirements in agriculture. In my fourth chapter I implement and adapt the hyperspectral sensing, multispectral imaging and machine learning image analysis developed in the third chapter to detect asymptomatic (and symptomatic) Z. tritici infection in winter wheat, in UK based field trials, with high accuracy. This has the potential to improve detection and monitoring of all stages of Z. tritici infection and could facilitate precision agriculture methods to be used during the current growing season that optimise fungicide use and increase yield.

Judaism has an oral and written tradition going back over 3,500 years. Core to this tradition are the stories of how our prophets, Judges, Kings and ordinary Jewish men and women have led the Jewish people including with the principles of Tikkun Olam (social justice), Chesed (acts of loving kindness) and Tzdacha (righteous giving). This research presented in this thesis builds a reflexive practitioner-based model founded in Judaism and 40 years RAF and Industrial experience. The model, to be called 20/20 LEADERSHIP, is offered as a set of principles or practical signposts particularly for new leaders wishing to build a participatory leadership practice to drive organizational development and operational excellence. The model was developed using a multi-domain approach in Jewish and secular environments. Reflexive Thematic Analysis (RTA) using literature and a focus group developed the model of 12 key principles. The model was then tested using a Perception Survey in an environment of Participatory Action Research (PAR) to measure the impact of the model to effect business improvement. Further RTA were used to ascertain the utility of the operationalization of the model. These RTA also report changes by leaders to their evolved leadership practice and changes in attitudes in that practice during the reported business improvement. Though the model proved largely successful, this paper discusses the limitations of using 20/20 LEADERSHIP and PAR in changing an organization from the perspective of the middle manager. The paper concedes that 20/20 LEADERSHIP has similarities with elements of other models but that 20/20 LEADERSHIP concepts based in Judaism's 3500-year history predate these modern models. The thesis explores how coaching, and mentoring are force multipliers for organizational development when used as a means of operationalising the new model. The uniqueness of the study lies in building a secularized model, operationalized through the vehicle of a new model of PAR that combined the author's experience of Judaism, military service, and senior industrial leadership in promoting organizational development and operational excellence. Such a model is currently absent from the leadership literature.

This study centres on the choices of Language Learning Strategies (LLSs) employed by Chinese and Taiwanese students learning English in a Taiwanese faith-based university in the Republic of China (ROC). LLSs have been extensively researched in the fields of English as a Foreign Language (EFL) and English for Speakers of Other Languages (ESOL) mainly in the Global North. Although the definition of LLSs has been controversial for the last three decades, the concept has been widely used in the field of language learning. During my four and a half years of teaching in higher education institutions in China, I observed that my Chinese students in a Chinese university were often reluctant to volunteer answers to teacher-posed questions, participate in oral activities or challenge my thoughts and propositions. The focus on completing grammar-based tasks for exam preparation, and the lack of oral practice, resulted in students struggling to maintain a conversation where clear communication was achieved. Motivated to help my students in their language learning journey, I sought to better understand the strategies they adopted when learning English. My unforeseen relocation to Taiwan, and the augmentation in the Cross-Straitization of Higher Education, opened the way to research both Chinese and Taiwanese university students studying together in a Taiwanese university. Chinese and Taiwanese students are perceived to emanate from a Confucian Heritage Culture (CHC), however, their educational experiences prior to entering higher education, are different. This Mixed Methods study explores the LLS choices of both Chinese and Taiwanese students, together with the views of their teachers, through a cultural lens. The findings appear to show a lack of understanding by teachers and students regarding the utility of LLSs in the teaching and learning of English. Where Chinese students appear to employ LLSs, they utilise a limited range, acquired through repetition, in preparation for examinations in high school. Taiwanese students, under similar academic circumstances, appear more confident in their approach to language learning, having reported to experience more diverse curricula and opportunities to engage with speakers of English. Both cohorts participate in activities which appear to contribute to their development of English proficiency, but they do not recognise them as LLSs. Prior educational experiences play a role in students' selections of working partners and consequently has implications for student working groups. The supportive nature of this faith-based campus environment influences the language learning experiences of students. However, this influence does not appear to be recognised or proactively utilised.

Within the endoplasmic reticulum (ER) of higher eukaryotes, the unfolded protein response (UPR) plays an essential role in restoring protein homeostasis during ER stress. This pathway is mediated by three core proteins, PERK, IRE1 and ATF6. The ER chaperone, BiP, has been suggested to act as an ER stress sensor by dissociating from the luminal domains of these UPR sensors upon binding to misfolded proteins, leading to UPR activation. Perturbation of this mechanism has been implicated in an array of cancers and neurodegenerative diseases, however, due to the experimental challenges in ATF6 protein production, structural and mechanistic understanding of ATF6 is lacking. Therefore, this thesis aimed to optimise the synthesis of ATF6 luminal domain (ATF6LD) and to investigate the hypothesis that it shares the same mechanism of activation observed for PERK and IRE1. Furthermore, structural insights into ATF6LD and PERK full-length (PERKFL) were pursued using electron microscopy (EM) to better understand their biological function and facilitate therapeutic strategies. Extensive optimisation resulted in the successful expression and purification of native ATF6LD that was shown to adopt two distinct glycoform populations in the ER. In vitro biophysical studies identified a high affinity (Kd = 0.13  0.02 M) interaction between ATF6LD and the nucleotide binding domain (NDB) of BiP, indicating a shared non-canonical mode of binding, as previously proposed for PERK and IRE1. Low resolution EM analysis revealed the first structural insights of ATF6LD and showed that in the absence of BiP, ATF6LD can form a ring-like homo-trimer/tetramer complex that may play an important functional role. The novel synthesis of soluble PERK enabled interaction studies which showed binding of PERKFL and a megacomplex, consisting of the 80S ribosome and translocon members. Cryo-EM structural analysis of the 80S ribosome and a suspected PERK density at the P-stalk was determined at 2.9 Å. Occupancy of this density was questioned at high resolution and the exact binding site of PERK remains to be determined. Data analysis also identified dynamics of the 40S subunit between POST translation and idle state ribosome populations revealing a pincer-like movement that blocks the ribosome E-site. The results of this thesis reveal novel insights into the biological function of ATF6 and PERK. Developments in ATF6LD production and EM analysis will pave the way for further high resolution structure determination. The discovery that ATF6LD binds to the NBD of BiP significantly adds to our understanding of its mechanism of activation and provides an opportunity for designing new therapies. Binding of PERKFL to a translocon megacomplex suggests a link between the UPR and co-translational machinery.

In recent years scholarship has assumed that human interest in climbing mountains for any reason other than necessity began only in the eighteenth century, and that prior to this period humans avoided mountains as vile and dangerous places. This thesis seeks to contest these opinions by exploring the representation of mountains in classical and biblical texts and their influence on the mountain ascents of Egeria in the fourth century, of Saint Willibald in the eighth century and of Petrarch in the fourteenth century. Analysis of these ascents will allow for nuance and qualification of the received narrative regarding pre-Petrarchan perceptions of mountains. The introduction will examine what a mountain is and means, followed by a focus on the perception of mountains in classical literature. By attending to the representation of mountains in their classical texts, the chapter will show how a mountain could provide a positive framework of order, stability and safety; or portray aspects of disorder, chaos and danger. The chapter will show how imitation and emulation shaped mountain descriptions and perceptions. The next chapter will shift to perceptions of mountains in the Old Testament, mountains of theophany, covenant and homeland; the chapter will show how Egeria relied on the Bible for her travels in the Holy Land; and it will explore stories of Jesus on mountains in the New Testament, and the treatment of these stories by different authors, showing the significance of earlier writings for the shaping of perceptions of mountains. The thesis will then turn to Hugeburc's account of Willibald's climb of Mount Vulcano, and will examine his climb and her account in relation to earlier perceptions of mountains. The concluding chapter will use Petrarch's ascent of Mont Ventoux as a point from which to look back at the discussion of mountains within the thesis.

Colorectal surgery is the specialty of operating upon the bowel for a variety of reasons, the most common in the elective setting being bowel cancer. Bowel cancer operations involve careful planning, to ensure that the patient is being offered the most likely chance of cancer removal with a low chance of recurrence, balanced against the potential adverse effects of potential over treatment. This includes being able to effectively determine if a patient has disease from their primary bowel cancer spread to other areas of the body, most commonly the liver and lungs. This assessment utilised radiology scans, usually Computed Tomography (CT) scans to do so, however the results can occasionally be inconclusive. During colorectal surgery segments of bowel are removed, and often the remaining bowel joined together again to restore bowel continuity, named an anastomosis. Whilst these joined when first formed are water-tight, around 1 in 20 will not remain so, with part or all of this anastomosis failing to heal, which allows the bowel contents to leak into the surrounding tissues causing initially a local infection and eventually overwhelming sepsis. This process of events is called an anastomotic leak, and if it occurs the chance of the patient dying within a month of their surgery increases by a factor of 20. If that patient survives then sadly, they are still at risk of lifelong worse bowel function and quality of life, a longer hospital stay, and even a higher chance that their original bowel cancer will return. Trying to determine which patients are developing an anastomotic leak is difficult - it often starts nebulously and can mimic many other post-operative complications, such as an irregular heartbeat or chest infection. Sadly, the longer the time taken to diagnose an anastomotic leak, the worse for the patient, with associated mortality rapidly increasing from 5 days following an operation, but it is exactly during this early post period when so many conditions may mimic a leak and vice versa. Even a 24-hour delay in management is associated with a tenfold increase in mortality. CT scanning forms a critical component is assessing patients with complications following bowel surgery, especially in the context of trying to diagnose an anastomotic leak. Even with the most rigorous investigation there is always the potential for both false positive and false negative results. A false negative result can cause a significant delay to subsequent diagnosis and management of an anastomotic leak, with associated mortality from 5 to 45%. Artificial Intelligence, namely Artificial Neural Networks provides a novel way to approach these clinical situations, adopting machine learning to the clinical field to augment and improve the clinician's judgement at moments of uncertainly. The focus of this thesis is that of improving outcomes of patients with colorectal disease incorporating artificial neural networks as one of the main tools to do so.

The circular economy concept is becoming more important against a backdrop of increased population growth and prosperity, ultimately resulting in the growth of the unsustainable use of the Earth's resources, with much of this ending up as waste with little or no value. The building sector through its provision of homes, schools, hospitals and places of work is by far the greatest consumer of resources and producer of waste when compared to other sectors. Whilst the sector has successfully achieved high recycling rates, most of this waste is downcycled where the value, quality and functionality are lower than the original product; moreover, the resources, that the sector uses are largely from primary sources and material costs are rising. Whereas sustainable buildings have been receiving growing attention in the last decade, there has been less focus on the circular economy. Policymakers and industry are starting to recognise these concerns by the development of various circular economy strategies, action plans and roadmaps; however, progress is slow. Circular economy in the building sector means that buildings should be designed to create minimal waste by being long-lasting, allowing them to be easily repaired and refurbished, and to be deconstructed at end of life, so the products and materials within can be reused or recycled, maintaining their value, where possible. Whilst there are an increasing number of circular economy academic and practitioner studies published, its implementation is still in its infancy and research is fragmented. Specific sector frameworks are needed to assist in implementing circular economy and whilst a few have been developed in the building sector, they largely focus on one or a few circular economy aspects and on one or a few stages of a building or supply chain stakeholders, even though the various benefits of encompassing all these aspects are evident. Hence, this research sought to fill this gap with an aim to examine the concept of circular economy within the context of the UK building sector. It also explored how a circular economy can be implemented for a building project, covering the whole lifecycle. This was achieved through the development of an industry reviewed framework. The research was based on a mixed method design employing a variety of data collection techniques which complemented and built on each other. From a literature review, the existing circular economy theories, principles and approaches and their current and potential applicability in the building sector were investigated, as well as barriers and enablers. These findings were developed further by investigating how these applied in practice, with a snapshot undertaken for the UK building sector based on an industry questionnaire, resulting in 110 responses, together with 4 focus groups at an industry event, with 97 attendees. This provided much quantitative data on the current state of play and the perspectives of key stakeholders, together with the relative importance of the barriers and enablers and insightful qualitative data on the trends and relationships. An in-depth investigation was undertaken to establish how circular economy approaches in the building sector could be adopted through the development of critical success factors (CSFs). This was undertaken through a supply chain workshop with 25 representatives who identified and clustered CSFs, resulting in the identification of eight thematic CSFs. To enable a greater understanding of how these could be implemented at a building project level, semi-structured interviews were held with 13 participants, representing the typical parts of a supply chain. This was complemented with a pre-interview questionnaire, in which the interviewees ranked the CSFs for priority, timescale and ease for implementation, which formed the basis for discussion. This resulted in the identification of 56 CSF subfactors. Also examined was the potential of applying circular economy principles to building types and lifecycle stages, and the level of stakeholder influence. This data culminated in the development of a circular economy framework with multiple levels encompassing the sectoral barriers and enablers and their inter-relationship, and at a building project level, the CSFs and subfactors, cross-linked to the enablers. An industry review was undertaken on the framework through a questionnaire and focus group. Data was obtained at this focus group for which project lifecycle stages each CSF subfactors should be implemented and which stakeholders should be involved, and who should lead. This research has provided the novel contribution of how circular economy aspects can be applied in the building sector, from firstly a sector perspective and secondly a project perspective. This includes the categorisation and relationship of sectoral barriers and enablers, which translate into detailed CSFs and subfactors at a project level, to be implemented across a project's lifecycle, for all aspects of material circularity, involving the key parts of a project supply chain. This framework can be used as a platform for the sector to move towards a more circular built environment.

Tuberculosis (TB) is the leading cause of death from a single infectious agent, with a staggering 10 million people estimated to have contracted the disease in 2019 alone. Whilst treatments for TB exist, continual emergence of drug-resistant strains necessitates urgent development of next-generation antituberculars. A promising new target is the essential glycolipid exporter mycobacterial membrane protein large 3 (MmpL3), a member of the resistance-nodulation-division (RND) superfamily. MmpL3 is required for construction of the distinctive Mycobacterium tuberculosis (Mtb) cell envelope; a complex lipid-rich assembly critical to mycobac- terial viability. Despite discovery of numerous MmpL3 inhibitors, including one in clinical trials, a structural understanding of the transporter, and by extension the variants identified to confer resistance to said experimental agents, has remained elusive. To this end, the research herein presents a 3.0 Å reconstruction of Mtb MmpL3; the culmination of a project structurally pursuing the RND exporter through construct design & characterisation, in vitro binder selection, nanodisc reconstitution, in meso & in surfo crystallisation trials, and imaging by Cryo-EM. Unexpectedly monomeric, the Mtb MmpL3 atomic model provides insights into the evolutionary co-option of RND architecture for lipophile transit. Most notably, the protein houses an extensive periplasmic cavity with putative functional rel- evance as the glycolipid translocation conduit. A detergent molecule resolved within the cavity plausibly sheds light on interactions employed by MmpL3 to coordinate its native substrate. Additionally, comprehensive mapping of known resistance-conferring substitutions suggests the existence of at least two routes, operant within different domains, by which antituberculars inhibiting MmpL3 can be mutationally circumvented. Taken together, the data reported in this thesis set the stage for an era of structure-based drug design against MmpL3; guided by an enhanced appreciation of the underlying resistance landscape.

In this thesis, I present results from population studies conducted on galaxies across most of cosmic time. Using the unique depth and area combination of modern, ground-based surveys allows for strong constraints to be placed on the number density of the most massive and luminous galaxies between redshifts of 0.1 < z < 5.2, while simultaneously allowing for contextualisation of results with the fainter/lower-mass population. The dataset compiles together ~ 2,000,000 objects over 6 square degrees of the sky and I use these to tackle two issues facing extragalactic research. First, I measure the stellar mass function of galaxies from 0.1 < z < 2.0, covering the peak of global star formation (z~1.5-2.0). A sample of 320,000 galaxies is used to map the exponential cut off in galaxy number density at high masses. The survey area used allows for variance attributed to large scale structure in the Universe to be significantly reduced compared to similar studies in the past and provides evidence this exponential cut off in galaxy number density shifts to greater masses with time, matching predictions from some hydrodynamical simulations such as EAGLE. I suggest this is driven by an increasing population of massive, passive galaxies produced by mergers. Second, I measure and examine the ultraviolet luminosity function of galaxies in the redshift range 3.5 < z < 5.2. With high precision over the luminosity range in which the dominance of ultraviolet emission transitions from galaxies to active galactic nuclei (AGN), I find that both the Schechter function and double power law models can be used to describe the galaxy population. However, they predict drastically different number counts for ultra-luminous galaxies (M_{UV} < -23). Alongside, I find the number density of faint AGN (M_{UV} > -24) are high, generating a steep power law slope -2.1 < αAGN < -1.7. I propose that the large rise in space density of AGN over this time period can be attributed to a global increase in the number density of active black holes. Measurements of the galaxy population are found to match models which suggest that a steep bright-end slope is driven by dust obscuration and that mass-dependent quenching from AGN feedback is not yet significant at this time.

This thesis covers the design of a metal hydride reactor within a thermo-chemical energy store for use in concentrated solar power (CSP). Thermo-chemical energy storage has been explored to improve on existing sensible heat technologies, potentially enabling fulfilment of CSP thermal energy storage cost targets, where metal hydrides have emerged as a TCES front-runner. This work introduces a unifying model for both the hydrogenation and dehydrogenation kinetics of MgH2, through the Site Availability Model (SAM). The model expands on Langmuir's site theory, in which a site can also be unavailable or available to react. This "unavailability" is governed by the site availability driving force, incorporating ideas such as site de-activation and strain/relaxation, which is influenced by temperature and pressure. These phenomena are proposed for both hydrogenation and dehydrogenation. In addition, SAM assumes the rate determining step is at the surface, where both hydrogenation/dehydrogenation assume a spherical surface, with dehydrogenation including the concept of particle fragmentation. The models developed, SAM:DR and SAM:ACR:SC:F, were successful in representing the kinetics of Mg hydrogenation and MgH2 dehydrogenation respectively of a small 0.2g sample, for all conditions tested. This includes conditions at close and moderately far from equilibrium for Mg hydrogenation. The SAM was also successfully applied to a 154g magnesium sample, providing confidence that the derived rate laws exhibit intensive characteristics, and assurance that the models can be used for larger scale reactor design. The implications of the thesis demonstrate the advancement in reactor design for metal hydride thermo-chemical energy storage to enable larger scale reactor designs. N.B. COVID-19 did not majorly impact the project completion, however it did disrupt the experiments on the large lab-scale reactor (chapter 6). The duration of the delay was approximately 3-4 months. It would have been desirable to run more tests and explore ways to achieve a higher operating temperature. In general, it was possible to fulfil the aims and objectives of this thesis.

In recycling the obsolete term Pastorical, this practice research submission comprises an original five-act play, Besieged, and an exegesis exploring the impact of pastiche historical dialogue on an audience. Besieged is a play about events in Portsmouth in 1642 at the beginning of the English Civil War. Responding to the provocation from some authors and critics that pastiche is a pejorative term to describe an empty and inert practice, the production of the play explores whether pastiche historical dialogue can elicit politically reflective and affective responses. The process of drafting, workshopping and rehearsing the play was designed to generate feedback to enable redrafting in consideration of the impact of the pastiche. Chapter One begins by using Robin Nelson's theories of practice research to develop a model for the project. The status of pastiche is then explored, including Richard Dyer's assertions that it is compatible with affect, and a development of Brecht's Verfremdungseffekt is posited. Reception theory is also considered in relation to cognitive studies and playwrights' assumptions. Chapter Two eavesdrops on the language of 16th and 17th century drama and the development of genre in relation to the use of pastiche. Chapter Three chronicles the method used to create Besieged, involving research of the blank verse and prose of English drama in that period, the historical research of the play, and the resources available to enable the pasticheur to assimilate the style. Chapter Four analyses the feedback cycle with examples of the development of the dialogue, and Chapter Five analyses the full range of audience feedback. Chapter Six explores the rhythm and metre of English Renaissance Drama to establish further techniques to improve the writing. The Conclusion makes the case that pastiche historical dialogue can simultaneously engage empathy and create a critical distance and provides a taxonomy for Pastorical Drama.

Each year hundreds of millions of dollars are invested in corporate communication technologies worldwide in the hopes that this investment will create more productive employees and in turn, an edge in the marketplace. As the workforce moves more and more from the traditional working space to the virtual workplace, it behoves corporations to become mindful in terms of the effects of technologies they wish to invest in and why. Could the lack of engagement or sporadic and insufficient interaction impact the quality and rate of production? Conversely, can the over usage of communication technologies inhibit productivity? If so, how does technology play a role in influencing this phenomenon? This study investigates the efficacy of various types of technologies and their usage in the virtual workplace. Specifically, how frequency and methods of communication via a variety of technological tools impact the quality and quantity of production in asynchronous, non-collocated virtual work teams. The research design incorporates the case study strategy in examining an educational corporation whose primary, though not sole, purpose is to provide evaluations for constructed responses to prospective students entering university. The theoretical framework for this paper utilises the environment-person fit theory as it applies to the technological milieu and individual relationships to the virtual workplace. Data was collected through an initial set of semistructured, in-depth interviews utilized to determine how communications can be improved in the virtual teams. This set of interviews was subsequently followed up by three Action Cycles and mini-dialogues to determine the best tools to implement in order to achieve the optimal results in production quality and quantity. The initiation of such an investigation could allow for continued monitoring of efficacy in both existing technologies as well as integrating new technologies in the future – a process and internal evaluation mechanism that was previously lacking in our corporate milieu. The study revealed several aspects of the complexities of virtual communications. Overwhelmingly, leadership played a crucial role in the participation and willingness of the virtual team to engage and become proactive, regardless of the technological tools used. The optimal frequency of communication preferred proved to be a bit more elusive to specifically pinpoint, though the main finding here was indicative of purposefulness rather than frequency or a specific number of contacts throughout a shift. Preference of specific tools was found to be across the board as team members preferred those tools that were convenient, less intrusive of their work, and were embedded into the platform rather than those external to our system. These results were reflected in both the quantity and quality of production. As a direct result of this study, specific internal actions were taken and broader industry level recommendations were made accordingly. And finally, this research opens the door to a whole host of further considerations and future research questions, such as; technical investment, advantages and disadvantages of virtual teams, a cost-benefit analysis of various types of technologies, and the examination of management styles and the usage of technology in corporate educational settings.

Ischaemia-reperfusion injury (IRI) is an unavoidable consequence of deceased-donor kidney transplantation that has a profound effect upon both immediate and long-term graft function. Disruption to microvascular perfusion (MVP) and tissue oxygenation (PtO2) are central to the development of IRI, but detailed regional pathophysiology remains unresolved in the context of renal transplantation. Normothermic machine perfusion (NMP) is a novel preservation technology that aims to improve pre-implantation kidney quality, but may also be used experimentally to investigate transplant reperfusion. My PhD set out to determine the optimal perfusion conditions to improve kidney quality, and to investigate the underlying heterogeneity in pathophysiology within regions of the kidney which may impact kidney quality. Firstly, we used a porcine model of donor kidney retrieval, NMP, and simulated reperfusion to test the hypothesis that reducing current NMP perfusate oxygenation (PPO2) from superoxic levels would improve renal function and reduce reperfusion injury. In kidneys exposed to either short or long cold ischaemic times, reducing PPO2 from the clinical standard to normoxic or hypoxic PPO2 altered oxygen kinetics during NMP but did not influence tubular function, clearance, urine output, or biomarkers of renal injury during simulated reperfusion. Secondly, we used porcine and human models of transplant reperfusion to test the hypothesis that the renal medulla would be disproportionately affected by tissue hypoperfusion, hypoxia and acute inflammation. In a porcine reperfusion series, PtO2 and MVP were significantly altered following IRI when compared to pre-ischaemic baselines, with greater variation and heterogeneity seen in the medulla than in the cortex. In a human reperfusion series, there was widespread initial microcirculatory disruption, persistent lower medullary PtO2 and a distinct medullary inflammatory environment. In summary we have described novel porcine and human renal medullary physiology and inflammation during transplant reperfusion that highlight the need for medulla-specific strategies to ameliorate IRI. We have further determined changes to renal physiology and injury in response to perfusate oxygenation in a novel preservation technology that may guide clinical implementation.

This thesis examines the legal notebooks of law students at the early modern Inns of Court, from 1575 to 1620. These notebooks were practical tools of learning in which serious-minded students recorded their formal legal studies. This study is specifically focused upon the non-legal texts that are often found written into these otherwise strictly legal notebooks. For the purpose of this study I define non-legal texts as those texts not obviously related to formal legal study at the Inns. These non-legal texts include classical, scriptural and contemporary histories, humanist literature, humorous stories, verse composition and philosophy. These notebooks have mainly been studied by legal historians with an eye to reconstructing the day-to-day educational practices of Inns members. Literary scholars have occasionally focused upon the literary parts of notebooks such as these, but they have not considered the wider, legal context in which those non-legal texts were written. There has previously been no sustained study on the non-legal, literary contents of legal notebooks belonging to law students at the Inns of Court. Through close textual and material analysis, I treat these notebooks as whole, composite objects. I question why these non-legal texts were included in otherwise vocational and educational legal notebooks, and whether their authors perceived a relationship between their formal legal studies and these non-legal texts. My research challenges our current understanding of what constituted a legal text in the early modern period. I argue that these non-legal texts were used to supplement the self-directed legal educations of committed and serious law students. In doing so I propose that those students use of literature and play in their notebooks was an adaptation of humanist educational practices that was entirely unique to the Inns of Court.

This folio of creative works is comprised of a set of installations and fixed-media audio works composed between January 2017 and December 2019. The works in the folio take inspiration from a variety of ideas in club cultures and visual arts that are hybridised to form my approach to creative practice. The motivation behind the creative work is to closely examine the similarities between club culture and the visual arts, particularly in relation to notions of site, interaction and participation. The resulting works employ a variety of materials and disciplines in their creation, including techniques from artistic practices and material gathered from participants, collaborators and sources of personal inspiration in music and the visual arts. The submitted work aims to create work that is not for the club, but about the club, through the lens of my own embodied experiences and those of participants in club spaces and club culture.

Ice-nucleating particles (INPs), a small fraction of the overall atmospheric burden, are responsible for heterogeneous ice nucleation in the atmosphere. INPs have the potential to catalyse ice formation in super-cooled cloud droplets, thus are able to influence cloud properties and radiative effects. Despite the importance of INPs, our knowledge of their spatial and temporal variation in the atmosphere is poor, limiting the predictive capacity of climate models. This thesis aimed to improve the knowledge surrounding atmospheric INPs through their measurements and characterization, but also through the development of instrumentation by which to do so. The Portable Ice Nucleation Experiment (PINE) chamber was developed in order to meet the technical needs required to answer important questions about the abundance of INPs in our atmosphere. PINE is a portable INP counter capable of making measurements autonomously, with a high-time resolution across the entire temperature regime of mixed-phase clouds. Upon completion of the first PINE prototype, PINE was deployed to the Hyytiälä forestry research station with the goal of validating it in a field environment, and also quantifying the INP concentrations in a boreal environment. A series of field and laboratory studies were carried out in order to improve our knowledge of the distribution and properties of INPs in the atmosphere. Combustion aerosol generated during Bonfire Night celebrations in the U.K. was shown to be an ineffective ice nucleator, unable to compete with ambient INPs. Viruses were shown to potentially play a role in atmospheric ice nucleation in marine environments, whilst the INPs responsible for greater than expected concentrations in a boreal forest environment were characterized through wet-dispersion experimental techniques. Overall, this thesis serves to further our understanding of INP concentrations in the atmosphere through space and time, and elucidate the nature of the aerosol particles responsible. Further to that, the techniques and instrument development described here will aid in furthering this understanding through robust experimentation.

This portfolio thesis comprises of three parts: a systemic literature review, an empirical paper and the corresponding appendices. Part one is a literature review exploring the literature surrounding the development and maintenance of the therapeutic relationship between patients, families and health care professionals in type 1 diabetes. The results suggest a variety of factors which affect the development and maintenance of the therapeutic relationship primarily from the parents and young adult's perspectives. Part two is an empirical paper which investigated compassion fatigue and compassion satisfaction in professionals who work with children with type 1 diabetes. Using an online survey and quantitative methodology, the following information was collected: profession, years working in diabetes, caseload size, percentage of caseload classed as complex, percentage of caseload with HbA1c above 69 mmol/mol and personal stressors. General linear regression models were completed with all work related factors not statistically significant apart from personal stressors. Part three has the Appendices from part one and two.

Introduction: In recent years, there have been sustained concerns about suicide amongst UK university students. Despite increasing demand for services for students in severe emotional distress, students may not be accessing support services. This study aimed to identify barriers to, and predictors of, mental health service access for suicidal university students in the UK. Finally, this study also explored ways in which support for suicidal students could be improved. Methods: A mixed-methods approach was employed in this two-phase study. Content and thematic analyses of interview transcripts were considered alongside current literature in order to develop (in collaboration with students) an online survey asking UK university students about their life experiences, attitudes about mental health stigma and help-seeking, and utilisation of support services. Students also gave suggested improvements for services supporting suicidal students. Results: Commonly reported barriers to help-seeking amongst students were uncertainty around the seriousness of one’s needs and long waiting times. Personal contact with service users, perceived need for help, help-seeking intention and stigma were all found to be associated with suicidal students accessing support. Students commonly suggested services should ensure accessible, safe and varied provision to support students with suicidal ideation. Conclusions: This study has highlighted personal experiences and attitudes which predict service use, including previous social contact with service users, perceived stigma, and self-stigma. A number of frequently endorsed personal and institutional barriers preventing suicidal students accessing services were identified. These findings were discussed in the context of students’ suggestions for improved service provision.

The current study investigates the effectiveness of international as well as national privacy tort laws in protecting the privacy rights related to personal information exchanged during cyber transactions. The focus is on exploring potential answers to the question: “how to regulate privacy in the digital age?” by elaborating on the conceptual, technological, and legal challenges of the phenomenon of cyber privacy. Firstly, the study demonstrates the complexity of defining the concept of ‘privacy’ across time and space – here it is argued that the lack of sufficient awareness of the meaning of ‘privacy’ and the absence of a universal consensus on what constitutes a ‘privacy right’ by citizens of the Internet, e-commerce and e-business organisations, and cyber laws legislators have significantly contributed to the breaches of consumer’s privacy laws. Secondly, the study identifies the contribution of the inherent technological challenges of digital platforms and the tempo-spatial nature of the cyber environment and its digital tools to the complexity of dealing with ‘privacy’ online, and consequently, to the difficulty of resolving disputes associated with online activities. Thirdly, the study elaborates on the legal difficulties associated with ‘cyber-jurisdictions’, which have often led to various conflicts of laws between national states. To demonstrate the boundedness of cyber privacy laws, the study has embarked on investigating both the EU and the US legal environments for dealing with the concept of ‘privacy’, the developing and protection of ‘privacy right’, the prosecuting of privacy protection breaches, and the violating of relevant laws. In doing so, the study has taken electronic commerce activities as its point of departure to investigate how businesses engaged in various forms of privacy breaches had escaped prosecution due to legal loopholes or lack of ability to implement state laws for e-privacy cases of a trans-border nature. Consequently, the study has demonstrated a dire need for having the political will of world states and the harmonisation of online privacy laws of those states in order to deal more effectively and appropriately with the right to privacy protection of personal information in the cyber environment. Otherwise, alternative approaches for internet governance need to be developed for resolving legal disputes of cyber nature.

Pancreatic Ductal Adenocarcinoma (PDAC) is characterised by a dense desmoplastic reaction that is attributed to the activation of pancreatic stellate cells (PSCs) in the stroma. This alteration of the tumour microenvironment is thought to contribute to PDAC aggressiveness and resistance to therapy. Recent studies have shown that exosomes (a subgroup of secreted extracellular vesicles) secreted by cancer cells facilitate cross talk between tumour cells and the microenvironment. However, the mechanisms that lead to the secretion of these vesicles remains elusive. Here, we report for the first time, a novel role for centrosome amplification, a common feature of human tumours, in the secretion of small extracellular vesicles (sEVs). We show that centrosome amplification significantly correlates with and is sufficient to induce the elevated secretion of sEVs in PDAC cell lines. Furthermore, we demonstrate that oxidative stress in cells with supernumerary centrosomes is the driving force behind this altered sEV secretion. An analysis of centrosome amplification-associated increases in cellular reactive oxygen species (ROS) demonstrated an impaired lysosome function and the prevention of MVB/lysosome fusion events. The results indicate that centrosome amplification induced ROS induces sEV secretion by preventing MVB degradation by the lysosome, shifting their fate to fusion with the plasma membrane and subsequent secretion of their intraluminal vesicles (ILVs) as exosomes. To understand if exosomes secreted from cells with amplified centrosomes could impact the tumour microenvironment, we subsequently investigated the role of these sEVs on the activation of PSCs, as measured by the formation of fibres containing alpha-smooth muscle actin (α-SMA). We found that sEVs isolated from cells with supernumerary centrosomes elicit significantly stronger activation of PSCs compared to sEVs isolated from cells with a normal centrosome number, suggesting a difference in their biological cargo. SILAC based-proteomic analysis revealed the gain or loss of 6 EV protein in sEVs isolated from cells upon the induction of centrosome amplification, that may have a role in the activation of PSCs. We hypothesise, that further understanding the role of centrosome amplification in sEV-mediated PSC activation may help us to identify innovative ways to block PSC activation and prevent the progression of PDAC, which could have major clinical implications for patients with this devastating disease.